Differences in innate immune function between allergic and nonallergic children: New insights into immune ontogeny

• Published in: Journal of allergy and clinical immunology Vol. 127; no. 2; pp. 470 - 478.e1
• Main Authors: Tulic, Meri K., Hodder, Megan, Forsberg, Anna, McCarthy, Suzi, Richman, Tara, D’Vaz, Nina, van den Biggelaar, Anita H.J., Thornton, Catherine A., Prescott, Susan L.
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01.02.2011; Elsevier; Elsevier Limited
• Subjects: Adaptive Immunity; Age Factors; allergens; allergic disease; Allergies; Allergy and Immunology; Antigen-Presenting Cells - immunology; Asthma; Biological and medical sciences; Case-Control Studies; Child, Preschool; children; Disease; Eczema; Female; Food; Food allergies; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Hospitals; Humans; Hypersensitivity - immunology; immunity; Immunity, Innate; Immunopathology; Infant; Infant, Newborn; Infections; innate immunity; interferon-gamma; interleukin-10; interleukin-1beta; interleukin-6; Ligands; Male; Medical sciences; ontogeny; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; T-lymphocytes; T-Lymphocytes - immunology; TECHNOLOGY; TEKNIKVETENSKAP; Toll-like receptor; Toll-like receptors; Toll-Like Receptors - physiology; tumor necrosis factor-alpha; innate immunity; APC; children; SPT; TLR; allergic disease; ontogeny; mDC; NK; Toll-like receptor; pDC; myeloid dendritic cell; Skin prick test; Plasmacytoid dendritic cell; Natural killer; Antigen-presenting cell; Human; Immunopathology; Allergy; Natural immunity; Toll like receptor; Immunology; Development; Child; Comparative study
• ISSN: 0091-6749; 1097-6825; 1097-6825
• DOI: 10.1016/j.jaci.2010.09.020

Microbial products are of central interest in the modulation of allergic propensity. We sought to explore whether allergic children show differences in microbial Toll-like receptor (TLR)–mediated responses over their first 5 years of life. Mononuclear cells isolated from 35 allergic and 35 nonallergic children at birth and 1, 2.5, and 5 years of age were stimulated with TLR2-TLR9 ligands to study innate immune function and with allergens or mitogen to assess adaptive T-cell responses. Cytokine production was measured by using Luminex multiplexing technology. Nonallergic children show progressive and significant age-related increases in innate cytokine responses (IL-1β, IL-6, TNF-α, and IL-10) to virtually all TLR ligands. This innate maturation corresponds with a parallel increase in adaptive T H1 (IFN-γ) responses to allergens and mitogens. In contrast, allergic children show exaggerated innate responses at birth ( P < .01) but a relative decrease with age thereafter, so that by age 5 years, TLR responses are attenuated compared with those seen in nonallergic subjects ( P < .05). This early hyperresponsiveness in allergic subjects fails to translate to a corresponding maturation of T H1 function, which remains attenuated relative to that seen in nonallergic subjects but is associated with a characteristic age-dependent increase in allergen-specific T H2 responses ( P < .01). Our findings suggest significant differences in the developmental trajectory of innate immune function in children with allergic disease that might contribute to the recognized differences in postnatal adaptive T-cell immunity.